Activity-dependent glassy cell mechanics II: Nonthermal fluctuations under metabolic activity

Area of Science:

• Cellular biophysics
• Non-equilibrium thermodynamics
• Cytoplasmic dynamics

Background:

• The cytoplasm, a crowded bio-macromolecular environment, behaves as a glassy material fluidized by metabolic energy.
• Understanding the cytoplasm as a non-equilibrium system is vital for linking cell mechanics to metabolic processes.
• Characterizing the relationship between metabolic activity and cellular mechanics remains a significant challenge.

Purpose of the Study:

• To investigate the relationship between cellular metabolism and cytoplasmic fluctuations.
• To determine whether nonthermal fluctuations in living cells are linked to active force generation or displacement.
• To establish nonthermal fluctuations as potential indicators of metabolic activity.

Main Methods:

• Active and passive microrheology experiments were performed on eukaryotic cells.
• Nonthermal fluctuations were quantified by assessing violations of the fluctuation-dissipation theorem.
• Cellular metabolic activity was experimentally regulated to observe its effects on fluctuations.

Main Results:

• Nonthermal displacement fluctuations, rather than active nonthermal forces, were found to be directly linked to cellular metabolism.
• Enzymatic activity was shown to generate meso-scale collective fluctuations, influencing cytoplasmic structural relaxations.
• Despite potential loss of autocorrelation at long timescales due to relaxation, displacement fluctuations remain regulated by metabolic reactions.

Conclusions:

• Metabolic activity directly regulates nonthermal displacement fluctuations in the cytoplasm.
• Nonthermal fluctuations, specifically displacements, serve as reliable indicators of a cell's metabolic state.
• The findings offer a new perspective on how metabolic energy influences cellular mechanics and dynamics.